In vivo lineage studies have shown that retinal cells arise from multipoten
tial progenitors whose fates are regulated by cell-cell interactions. To un
derstand the mechanism underlying their maintenance and differentiation, we
have analyzed the differentiation potential of progenitors derived from em
bryonic rat retina in vitro. These progenitors proliferate and remain undif
ferentiated in vitro in the presence of epidermal growth factor (EGF) and d
isplay properties similar to stem cells. In addition to expressing nestin,
the neuroectodermal stem cell marker, retinal progenitors are multipotentia
l. Upon withdrawal of EGF and addition of serum, the progenitors downregula
te the expression of nestin and express cell-type specific markers correspo
nding to neurons and glia. In addition to expressing cell-type specific mar
kers, retinal progenitors and their progeny could be distinguished on the b
asis of their distinct voltage gated current profile. A proportion of proge
nitors is lineage restricted and the fate of these cells can be influenced
by the microenvironment, suggesting that stage-specific interactions mediat
ed by the local environment influence the progression of progenitors toward
s acquisition of differentiated phenotypes. (C) 1999 Elsevier Science B.V.
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